The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
Research output: Contribution to journal › Journal article › Research › peer-review
ESSENTIALS: The lectin pathway's MASP-1/2 activates coagulation factors but the trigger of the activation is unknown. MASP-1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1-inhibitor. Activated platelets and fibrin were demonstrated to activate MASP-1 and MASP-2 both in vitro and in vivo. These findings may represent a crossroad between the complement and the coagulation systems.
SUMMARY:
BACKGROUND: The activated forms of the complement lectin pathway (LP) proteases MASP-1 and MASP-2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor in vitro. In vivo studies also show that MASP-1 is involved in thrombogenesis.
OBJECTIVES: To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions.
METHODS: Novel sandwich-ELISAs for detection of complexes between MASP-1 or MASP-2 and the serpins C1 inhibitor (C1-INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP-1 and MASP-2.
RESULTS: Activated platelets were shown by flow cytometry to bind Ficolin-1, -2 and -3 but not MBL, which was associated with activation of MASP-1 and MASP-2. We also demonstrated that fibrin and the plasmin-generated fibrin fragment DD in plasma, bind and activate MASP-1 and MASP-2. As demonstrated by the ELISA and SDS-PAGE/Western blotting, the fibrin-associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH were associated with markers of thrombotic disease and contact/coagulation system activation.
CONCLUSIONS: MASP-1 and MASP-2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions in vitro and in vivo, and may represent a novel activation/amplification mechanism in thromboinflammation.
Original language | English |
---|---|
Journal | Journal of Thrombosis and Haemostasis |
Volume | 14 |
Issue number | 3 |
Pages (from-to) | 531-545 |
Number of pages | 15 |
ISSN | 1538-7933 |
DOIs | |
Publication status | Published - Mar 2016 |
- Adult, Aged, Aged, 80 and over, Antithrombin Proteins, Blood Coagulation, Blood Platelets, Case-Control Studies, Complement C1 Inhibitor Protein, Complement Pathway, Mannose-Binding Lectin, Enzyme Activation, Female, Fibrin, Humans, Inflammation, Lupus Erythematosus, Systemic, Male, Mannose-Binding Protein-Associated Serine Proteases, Middle Aged, Multiple Trauma, Platelet Activation, Protein Binding, Signal Transduction, Thrombosis, Time Factors, Young Adult
Research areas
ID: 172399068